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Exp Clin Endocrinol Diabetes 2005; 113(6): 324-330
DOI: 10.1055/s-2005-865642
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Intense Cholesterol Lowering Therapy with a HMG-CoA Reductase Inhibitor does not Improve Nitric Oxide Dependent Endothelial Function in Type-2-Diabetes

A Multicenter, Randomised, Double-Blind, Three-Arm Placebo-Controlled Clinical TrialB. M. Balletshofer1 , S. Goebbel1 , K. Rittig1 , M. Enderle2 , I. Schmölzer3 , T. C. Wascher3 , A. Ferenc Pap4 , T. Westermeier4 , D. Petzinna4 , S. Matthaei1 , H. U. Häring1
  • 1Department of Endocrinology and Vascular Medicine, University of Tübingen, Germany
  • 2Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Germany
  • 3Department of Internal Medicine, Diabetic Angiopathy Research Group, University Graz, Austria
  • 4Bayer Vital GmbH, Leverkusen, Germany
Further Information

Publication History

Received: December 17, 2004 First decision: February 2, 2005

Accepted: March 17, 2005

Publication Date:
23 June 2005 (online)

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Abstract

Disturbances in nitric oxide (NO) metabolism resulting in endothelial dysfunction play a central role in the pathogenesis of atherosclerosis in hypercholesterolemia and in individuals with type 2 diabetes. It is unclear whether lipid lowering therapy with HMG-CoA-reductase inhibitors might improve endothelial function in subjects with type 2 diabetes as it is demonstrated in non-diabetic subjects with hypercholesterolemia. We examined the influence of 0.2 mg and 0.8 mg cerivastatin on endothelial function in a multicenter, randomised, double-blind, and three-arm placebo-controlled clinical trial. Endothelial function was assessed by nitric oxide-dependent flow mediated vasodilatation (FMD) of the brachial artery. A total of 103 patients with type 2 diabetes were enrolled in the study. Bayer Company undertook a voluntary action to withdraw cerivastatin from market, therefore the study was terminated earlier. At this point 77 patients were randomised, of which 58 completed the study (mean age 60 ± 8 years, HbA1c 7.4 ± 0.9 %). At baseline mean FMD was disturbed in all three therapy arms (5.18 ± 2.31 % in the placebo group, 3.88 ± 1.68 in the 0.2-mg cerivastation group, and 4.86 ± 2.25 in the 0.8-mg cerivastatin group). Despite a significant reduction in cholesterol and LDL-cholesterol-levels after 12 weeks of treatment (decrease in LDL-cholesterol - 26.8 ± 13.9 % in the 0.2-mg group and - 40.3 ± 16.0 % in the 0.8-mg group, p = 0.0001, ANCOVA) there was no difference in flow mediated vasodilatation (p = 0.52 and p = 0.56 vs. placebo, respectively, ANCOVA). HbA1c, CRP, and HDL-cholesterol did not change during the study. Furthermore no difference in safety profile between cerivastatin and placebo was found. Despite a significant improvement in lipid profile under statin therapy, no improvement of endothelial dysfunction in terms of nitric oxide bioavailability could be detected.

Key words

Endothelium - nitric oxide - brachial artery - atherosclerosis - diabetes - endothelial dysfunction - flow-mediated vasodilation - statin - ultrasound - vascular - vasodilation - placebo controlled - randomized clinical study - double-blind

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Bernd M. Balletshofer

Department of Internal Medicine/Endocinology and Vascular Medicine
University of Tübingen

Otfried-Müller-Straße 10

72076 Tübingen

Germany

Phone: + 49(0)70712982714

Fax: + 49 (0) 70 71 29 50 22

Email: Bernd.Balletshofer@med.uni-tuebingen.de